ArticleBlood2021
An alternate covalent form of platelet αIIbβ3 integrin that resides in focal adhesions and has altered function.
Article in Blood, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 15 papers.
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Who cites it
15 citing papers in PubMed, 19 citations in OpenAlex.
- Multiple disulfide-bonded states confer extensive conformational diversity in fibrinogen.Protein science : a publication of the Protein Society · 2026Article
- Using AlphaFold3 for the Interrogation of Protein Disulfide Bonds.Methods in molecular biology (Clifton, N.J.) · 2026Article
- Quantification of the Redox State of Protein Disulfide Bonds.Methods in molecular biology (Clifton, N.J.) · 2026Article
- Estimate of Numbers of Disulfide-Bonded Protein States.Methods in molecular biology (Clifton, N.J.) · 2026Article
- Quantification of the Redox State of Integrin Disulfide Bonds.Methods in molecular biology (Clifton, N.J.) · 2026Article
- Method for Selection of Antithrombin Disulfide-Bonded Subsets.Methods in molecular biology (Clifton, N.J.) · 2026Article
- Quantification of Site-Specific Disulfide Bond Redox States in Proteins by Parallel Reaction Monitoring-Mass Spectrometry (PRM-MS).Methods in molecular biology (Clifton, N.J.) · 2026Article
- Allosteric Disulfide Bridges in Integrins: The Molecular Switches of Redox Regulation of Integrin-Mediated Cell Functions.Antioxidants (Basel, Switzerland) · 2025Review
- Patient anti-FVIII drug antibodies bind preferentially to a subset of FVIII covalent states.Blood advances · 2025Article
- Differential transport pathways of saturated and unsaturated fatty acid esters in male mouse hepatocytes.Nature communications · 2025Article
- Transmembrane thiol isomerase TMX1 counterbalances the effect of ERp46 to inhibit platelet activation and integrin αIIbβ3 function.Research and practice in thrombosis and haemostasis · 2024Article
- Recent advances in vascular thiol isomerases and redox systems in platelet function and thrombosis.Journal of thrombosis and haemostasis : JTH · 2024Review
- Multiscale models of integrins and cellular adhesions.Current opinion in structural biology · 2023Review
- A Review of Methodologies for the Detection, Quantitation, and Localization of Free Cysteine in Recombinant Proteins: A Focus on Therapeutic Monoclonal Antibodies.Frontiers in molecular biosciences · 2022Review
- Emerging roles of platelets in cancer biology and their potential as therapeutic targets.Frontiers in oncology · 2022Review
Corrections and comments
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Authors and funding
6 authors at 2 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
The αIIbβ3 integrin receptor coordinates platelet adhesion, activation, and mechanosensing in thrombosis and hemostasis. Using differential cysteine alkylation and mass spectrometry, we have identified a disulfide bond in the αIIb subunit linking cysteines 490 and 545 that is missing in ∼1 in 3 integrin molecules on the resting and activated human platelet surface. This alternate covalent form of αIIbβ3 is predetermined as it is also produced by human megakaryoblasts and baby hamster kidney fibroblasts transfected with recombinant integrin. From coimmunoprecipitation experiments, the alternate form selectively partitions into focal adhesions on the activated platelet surface. Its function was evaluated in baby hamster kidney fibroblast cells expressing a mutant integrin with an ablated C490-C545 disulfide bond. The disulfide mutant integrin has functional outside-in signaling but extended residency time in focal adhesions due to a reduced rate of clathrin-mediated integrin internalization and recycling, which is associated with enhanced affinity of the αIIb subunit for clathrin adaptor protein 2. Molecular dynamics simulations indicate that the alternate covalent form of αIIb requires higher forces to transition from bent to open conformational states that is in accordance with reduced affinity for fibrinogen and activation by manganese ions. These findings indicate that the αIIbβ3 integrin receptor is produced in various covalent forms that have different cell surface distribution and function. The C490, C545 cysteine pair is conserved across all 18 integrin α subunits, and the disulfide bond in the αV and α2 subunits in cultured cells is similarly missing, suggesting that the alternate integrin form and function are also conserved.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.